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Formaldehyde → 1,1-Dimethylethyl (2R,6S)-2,6-dimethyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate

HRID 644700
Notes
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Reaction equation

HRID 644700 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][C@H:13]([CH3:15])[N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:11]([CH3:23])[CH2:10]2)=[CH:4][CH:3]=1.[CH3:24][C@H]1CN(CC2C=CC(NC)=CC=2)CCN1C(OC(C)(C)C)=O.[BH4-].[Na+].C=O.C[O-].[Na+]>>[CH3:23][C@@H:11]1[CH2:10][N:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([NH:1][CH3:24])=[CH:3][CH:4]=2)[CH2:14][C@H:13]([CH3:15])[N:12]1[C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 5

HCID 712FormaldehydeHCID 4311764Sodium borohydride2×HCID 10942334Sodium MethoxideHCID 592621311,1-Dimethylethyl (2S)-2-methyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylateHCID 592622361,1-Dimethylethyl (2R,6S)-4-[(4-aminophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylate

Product 1

HCID 59262220
1,1-Dimethylethyl (2R,6S)-2,6-dimethyl-4-{[4-(methylamino)phenyl]methyl}-1-piperazinecarboxylate

Conditions

Temperature
50 °C

Procedure

The title compound was prepared from 1,1-dimethylethyl (2R,6S)-4-[(4-aminophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylate (D8) using a method similar to that described for D3 in Description 3A although the reaction was heated at 50° C. for 48 h prior to addition of sodium borohydride then for 1 h after addition. Further paraformaldehyde (1 eq) and sodium methoxide (1 eq) were added; the reaction was heated at 50° C. for 12 h; further sodium borohydride (1 eq) was added and the reaction heated at 50° C. for 1 h. δH (CDCl3, 400 MHz) 7.16 (2H, d), 6.57 (2H, d), 4.05 (2H, m), 3.70 (1H, br s), 3.36 (2H, s), 2.82 (3H, s), 2.59 (2H, d), 2.06 (2H, dd), 1.49 (9H, s), 1.27 (6H, d). MS (ES+): 356.3 (MNa+), 234.3, no molecular ion (MH+) observed.

Workup

  1. additionfor 1 h after addition
  2. temperaturethe reaction was heated at 50° C. for 12 h
  3. temperaturethe reaction heated at 50° C. for 1 h. δH (CDCl3, 400 MHz) 7.16 (2H, d), 6.57 (2H, d), 4.05 (2H, m), 3.70 (1H, br s), 3.36 (2H, s), 2.82 (3H, s), 2.59 (2H, d), 2.06 (2H, dd), 1.49 (9H, s), 1.27 (6H, d)

Sources & evidence

ORD record
ord-2c6d87dc04a94f43815fc72b8eac5a57
Source dataset
uspto-grants-2010_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07700599B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes